INTRODUCTION
Childhood asthma is the most common chronic disease in childhood and a
significant public health problem in the U.S. as well as in many other
countries1. Despite relatively recent advances in our
understanding of the inflammatory nature of the disease and the
availability of highly effective medications to control their symptoms,
many pediatric patients continue to experience poor asthma control with
recurrent disease exacerbations2.
Acute asthma has a significant impact not only on the utilization of
health care and the quality of life of children and their families but
also on a large percentage of disease costs3. Recent
international evidence-based asthma clinical practice guidelines
recommend the use of inhaled beta-2 agonists (SABA) and systemic
corticosteroids (SC) as the first-line agents for acute
asthma4,5. The efficacy of SC in acute asthma is well
established, with a positive impact on several clinically meaningful
outcomes, such as hospital admission rate, symptom scores, and the
number of relapses after discharge from the emergency department
(ED)6. However, the fact that despite SC use many
children still require admission to hospital and that SCs have a slow
onset of action (3–4 h after their administration) is a cause of
concern among ED teams7.
For this reason, the use of other anti-inflammatory therapies such as
inhaled corticosteroids (ICS) for the treatment of acute asthma has been
explored6. Potential benefits of ICS in acute asthma
therapy might include a rapid onset of action and a significant efficacy
in diminishing airway reactivity and edema because of their direct
delivery to the airways8. This is mainly because ICS,
but not SC, cause immediate local bronchial mucosal vasoconstriction and
inhibition of edema formation mediated by non-genomic
mechanisms9. The main non-genomic mechanisms involve
the activation of endothelial nitric oxide (NO) synthase and NO
synthesis, which produce an increase in noradrenergic neurotransmission
in the airway vasculature, with a consequent reduction in airway blood
flow10. The decrease in airway blood flow is a
desirable effect in asthmatic patients, given that they have
significantly increased blood flow in the airway
mucosa11.
Therefore, the use of ICS for treating patients with acute asthma has
become a subject of interest in recent years. There are reports showing
the clear efficacy of ICS in the management of acute asthma when
compared with a placebo8,12. In a recent systematic
review with a meta-analysis that compared the efficacy of ICS with SC
for acute asthma in children consulting in the ED or the equivalent, we
found no significant differences between ICS and SC in terms of hospital
admission rates, unscheduled visits for asthma symptoms, or need for an
additional course of SC12. However, only a few studies
have investigated the possibility of a beneficial effect of ICS added to
SC, and the results have been conflicting, as was stated in a systematic
review published in 2012, where only two RCTs carried out exclusively in
a pediatric population were included8.
Thus the present systematic review aims at updating and evaluating the
available evidence for the efficacy of ICS (via nebulizer or metered
dose inhaler [MDI]) in addition to SC compared to the standard
therapy with SC for treating pediatric patients with acute asthma in the
ED or during hospitalization.